KR20090094384A - Thermal transfer methods and structures for microfluidic systems - Google Patents

Abstract

Processing devices that include one or more process arrays with thermal transfer structures that can be used alone or in conjunction with gravity/rotation to transport fluids within a microfluidic system. The thermal transport function can be accomplished by changing the temperature of one or more chambers to create a vacuum to draw fluids in selected directions within the process array. The methods and apparatus of the present invention may provide the ability to move fluids in a direction that is against the direction of gravity or any centrifugal forces generated by rotating a processing device using the thermal transfer structures. In other words, fluids may be moved against the direction of gravity or towards the axis of rotation using the thermally-activated vacuum.

Description

Heat transfer method and structure for microfluidic systems {THERMAL TRANSFER METHODS AND STRUCTURES FOR MICROFLUIDIC SYSTEMS}

The present invention relates to the field of microfluidic processing devices. More specifically, the present invention provides a method and apparatus for using a thermally-activated vacuum to transfer analytes in a microfluidic process array.

Devices in which various chemical or biological processes are performed are increasingly playing a role in scientific and / or diagnostic investigation. The chamber provided in such a device is preferably small in volume to reduce the amount of analyte required to perform the process.

One problem that persists with processing devices including chambers is the transfer of fluid between different features within the device. Conventional approaches to transferring fluid content between chambers often required human intervention (eg, manual pipette metering) and / or robotic manipulation. Such delivery processes suffer from a number of disadvantages, including, but not limited to, the potential for error, complexity, and associated high costs.

1 is a plan view of one exemplary processing apparatus according to the present invention.

FIG. 2 is an enlarged view including one process array as can be seen in the processing apparatus of FIG.

3 is an enlarged cross-sectional view of a portion of the processing apparatus of FIGS. 1 and 2 taken along line 3-3 of FIG.

4A and 4B illustrate an example process for delivering fluid using the example heat transfer structures of the process array of FIG. 2.

5 is a plan view of an example of a process array including chambers connected in series.

6 is a top view of another exemplary process array in accordance with the present invention.

7 is a cross-sectional view of one exemplary valve structure that may be used in connection with the process array of the present invention.

8-10 are plan views of another exemplary process array in accordance with the present invention.

11 illustrates a modular processing apparatus that can be used in connection with the present invention.

The present invention provides a processing apparatus that includes one or more process arrays having a heat transfer structure that can be used alone or in conjunction with rotation to transport fluid in a microfluidic system. The heat transfer function may be accomplished by varying the temperature of one or more chambers to create a vacuum to draw fluid in selected directions within the process array.

The method and apparatus of the present invention have the ability to move a fluid, among other potential advantages, in a direction against the direction of centrifugal force generated by rotating gravity and / or processing apparatus using a heat transfer structure. In other words, the fluid can be moved against gravity or towards the axis of rotation using a heat-activated vacuum. As used herein, the term “vacuum” refers to the pressure difference between the volumes in the process array that is large enough to move the fluid in the selected direction.

The heat transfer structure may also be used to control fluid movement within the processing device without requiring a physical valve structure that requires the opening or closing of the physical structure to allow fluid passage. For example, dimensions, geometries, materials, and the like can be selected such that fluid passage typically does not occur in the absence of a vacuum. One feature that may be used is a conduit that includes a fluid trap as described herein. In such cases, the heat-activated vacuum provided by the heat transfer structure can be used to control fluid movement within the process array.

In some embodiments, the heat transfer structure may include a heat drive chamber located in an area of the processing device spaced from the chambers in which fluid is transported therebetween. The spaced thermal drive chambers may be fluidly connected to the chambers in which fluid is conveyed between them by conduits formed in the device. One potential advantage of such structures is that the portion of the processing device that is heated (or cooled) to create a vacuum can be sufficiently removed from the chambers in which the fluid is transported therebetween, so that the analytes in the fluid being conveyed It does not significantly heat or cool as a result of heating or cooling of the drive chamber.

Heat transfer structures and methods may also be used to deliver (continuously and / or simultaneously) a plurality of discrete volumes of fluid into or through a chamber in a process array. Such control for fluid delivery can be used, for example, for washing to remove unwanted material from the sample, delivery of reagents at selected times and in selected amounts, and the like. When used to deliver multiple discrete volumes of fluid, the heat transfer structure can operate more effectively due to the presence of the liquid in the heat drive chamber where at least a portion of the liquid changes phase to become a gas. Such phase change can increase the volume change of the resident fluid caused by heating, and thus the resulting vacuum force can also increase as the retention fluid cools.

In one aspect, the invention provides a processing apparatus having at least one process array comprising a heat transfer structure comprising a first chamber and a retention fluid, wherein the heat transfer structure comprises a transfer conduit connected to the first chamber. Contains-; Providing an analyte in the first chamber; The first portion of the retention fluid in the heat transfer structure is heated through the delivery conduit by heating at least a portion of the retention fluid in the heat transfer structure such that the volume of the retention fluid in the heat transfer structure increases to pressurize the first portion of the retention fluid into the first chamber. Passing it through the analyte in the chamber; And cooling the heated retention fluid in the heat transfer structure after the first portion of the retention fluid has passed into the first chamber, wherein the volume of retention fluid in the heat transfer structure is reduced such that at least a portion of the analyte in the first chamber is reduced. A method for delivering fluid in the processing device by suction through the delivery conduit into the heat transfer structure.

The method of the present invention may optionally comprise performing two or more consecutive heating and cooling cycles on the retaining fluid in the heat transfer structure.

The method of the present invention may optionally include rotating the processing device about an axis of rotation while passing the first portion of the retention fluid to the analyte in the first chamber, wherein the rotation may cause the analyte to pass through the first chamber. Move toward the radial end. During rotation, the method may further include rotating at least a portion of the delivery conduit so that it is located closer to the axis of rotation than at least a portion of the first chamber.

The method of the present invention may include a heat transfer structure including a trap chamber in fluid communication with the transfer conduit, the heat transfer structure including a heat drive chamber in fluid communication with the trap chamber through the drive conduit and further comprising a transfer conduit. A portion of the analyte drawn through the heat transfer structure is deposited in the trap chamber. Residual fluid in the trap chamber may not be directly heated. The delivery conduit and drive conduit can be connected to the trap chamber on the radial proximal side of the trap chamber, such that fluid entering the trap chamber during rotation of the processing device is moved toward the radial end of the trap chamber to enter the trap chamber. Most of the fluid does not enter the drive conduit (substantially all of the liquid entering the trap chamber may not enter the drive conduit). The method may include rotating the processing device about an axis of rotation, wherein the radial proximal side of the trap chamber is located closer to the axis of rotation than the radial end side of the trap chamber.

In some methods, the delivery conduit may be connected to the first chamber at the first port, the first port being disposed at an intermediate position along the radial length occupied by the first chamber, the radial length being the axis of rotation of the rotary processing device. Along the radius extending from.

Some methods may include opening a valve located between the first chamber and the delivery conduit before passing the first portion of the retention fluid through the delivery conduit to the analyte.

The process array can include a second chamber and a second conduit extending between the second chamber and the first chamber, wherein the method includes removing fluid from the second chamber through the second conduit by rotating the processing device about an axis of rotation. The method further includes delivering to the one chamber. The method may further comprise opening a second chamber valve located between the second chamber and the second conduit prior to transferring the fluid through the second conduit from the second chamber to the first chamber. The processing apparatus may further comprise an intermediate chamber located between the second chamber and the first chamber along the second conduit, wherein the fluid transferred from the second chamber to the first chamber before the fluid reaches the first chamber. Passed into the intermediate chamber, the intermediate chamber includes a reagent located in the chamber, and the fluid contacts the reagent in the intermediate chamber before reaching the first chamber. The method may include opening an intermediate chamber inlet valve located between the intermediate chamber and the second chamber before passing the fluid from the second chamber to the intermediate chamber. The method may further comprise opening the intermediate chamber outlet valve located between the intermediate chamber and the first chamber before passing the fluid from the intermediate chamber to the first chamber.

In another aspect, the present invention may provide a processing apparatus including at least one process array formed within a body, wherein the at least one process array comprises a first chamber; A second chamber; And a process conduit extending between the first chamber and the second chamber, wherein the first chamber and the second chamber are upstream when moving from the second chamber toward the first chamber and from the first chamber to the second chamber. It defines the downstream direction when moving. The process array further includes a heat transfer structure comprising a heat drive chamber comprising a retention fluid and a transfer conduit extending between the first chamber and the heat drive chamber, the transfer conduit entering the first chamber through the transfer port; The delivery conduit includes a fluid trap in which a portion of the delivery conduit travels upstream between the delivery port and the heat drive chamber.

In some devices, the fluid trap in the delivery conduit reaches at least the midpoint of the first chamber between the first chamber and the heat drive chamber.

In some arrangements, a valve is positioned between the first chamber and the heat drive chamber, and fluid passage between the first chamber and the heat drive chamber through the delivery conduit is prevented until the valve is opened.

In some devices, the heat transfer structure further includes a trap chamber located along a transfer conduit between the first chamber and the heat drive chamber, wherein the trap chamber is located within the fluid trap or between the fluid trap and the heat drive chamber.

In some devices, the trap chamber is connected to the delivery conduit along the upstream end of the trap chamber.

In some devices, the heat transfer structure includes two or more heat drive chambers, all of which are located downstream of the fluid trap in the transfer conduit. A valve may be located between each of the first chamber and the thermal drive chamber, and fluid passage between the first chamber and each of the thermal drive chambers through the delivery conduit opens the valve located between the first chamber and the heat drive chamber. Until it is prevented.

In some devices, the process conduit is connected to the first chamber in a downstream direction from the delivery port.

In some arrangements, a valve is positioned between the first chamber and the process conduit, and fluid passage from the first chamber to the second chamber through the process conduit is prevented until the valve is opened.

In some apparatus, a plurality of process arrays are located within the body, the process array being substantially radially aligned around the center of the body such that the upstream and downstream directions extend substantially radially from the center of the body.

These and other features and advantages of the present invention are described below in connection with various exemplary embodiments of the apparatus and method of the present invention.

In the following detailed description of exemplary embodiments of the invention, reference is made to the accompanying drawings, which form a part hereof, and in which is shown by way of illustration specific embodiments in which the invention may be practiced. It is to be understood that other embodiments may be utilized and structural changes may be made without departing from the scope of the present invention.

The present invention provides a processing apparatus that can be used for the treatment of analytes. The analyte itself may be in fluid form (eg, a solution, etc.) or the analyte may be in the form of a solid or semisolid material carried in the fluid. The analyte may be incorporated into the fluid, such as in a dissolved state in the fluid. For the sake of simplicity, the term “analyte” is used herein to refer to any location in which an analyte can be located or positioned, regardless of whether the analyte itself is a fluid or contained within a carrier fluid (in dissolved state, suspended state, etc.). Will be used to refer to the fluid of. In addition, in some cases, an analyte may be used to refer to a fluid in which the target analyte (ie, the analyte to be treated) is absent. For example, wash fluids (eg, saline, etc.) may be referred to as analytes for the purposes of the present invention.

The analytes can be prepared with desired reactions such as PCR amplification, ligase chain reaction (LCR), self-sustaining sequence replication (3SR), enzyme kinetics studies, homogeneous ligand conjugation assays, and precise thermal control, for example. (Eg, isothermal processes sensitive to temperature changes) and / or may be processed in one or more chambers formed in the processing apparatus to obtain other chemical, biochemical or other reactions that may require rapid thermal changes. More specifically, the present invention provides a processing apparatus comprising one or more process arrays, each process fluid having an optional loading chamber, at least one chamber, a heat transfer structure, and a fluid between the various components of the process array. It may include a conduit for moving the.

As used herein, the term "chamber" should not be construed as limiting the chamber to the limited volume in which the process (eg, PCR, Sanger sequencing, etc.) is performed therein. . Rather, as used herein, a chamber is, for example, a volume that is loaded such that the material therein is subsequently transferred to another chamber when the processing device is rotated, the chamber in which the product of the process is collected, and the material is filtered. Chamber and the like.

Although various configurations of exemplary embodiments are described below, the processing apparatus of the present invention is described, for example, in US Patent Application Publication No. 2002/0064885 (Bedingham et al.); 2002/0048533 (Beddingham et al.); 2002/0047003 (Beddingham et al.), And 2003/138779 (Parthasarathy et al.); 2005/0126312 (Beddingham et al.); 2005/0129583 (Beddingham et al.); And US Pat. No. 6,627,159 B1 (Beddingham et al.) And US Pat. No. 6,987,253 B2 (Beddingham et al.). The above mentioned documents all disclose various different configurations of the processing apparatus that can be used to manufacture the processing apparatus according to the principles of the present invention. The device may preferably include fluid features designed to treat distinct microfluidic volumes of fluid, such as, for example, 1 milliliter or less, 100 microliters or less, or even 10 microliters or less.

Although centrifugal forces generated by rotation are described in connection with a rotating device that can be used to move the fluid in the conduit and chamber, the methods and devices of the present invention also relate to gravity (actual or induced) to move the fluid. Can be used, in which case the device itself does not need to be rotated. However, it should be understood that the apparatus and method of the present invention may in some cases rely on gravity and centrifugal forces (gravity and centrifugal forces act simultaneously or at different times) to move the fluid through the process array.

At least one aspect of the processing apparatus 10 may be described, for example, in US Pat. No. 6,734,401 (Beddingham et al.), Entitled ENHANCED SAMPLE PROCESSING DEVICES SYSTEMS AND METHODS; US Patent Application Publication No. 2007-0009391 A1 (Application No. 11 / 174,680), entitled "Compliant Microfluidic Sample Processing Discs" (COMPLIANT MICROFLUIDIC SAMPLE PROCESSING DISKS); Or base plate as described in US Patent Application Publication No. 2007-0010007 A1 (Application No. 11 / 174,757), entitled "SAMPLE PROCESSING DEVICE COMPRESSION SYSTEMS AND METHODS." It may be desirable to provide a surface that is complementary to the thermal structure device. In some embodiments, it may be desirable for at least one of the major faces of the processing apparatus of the present invention to provide a flat surface.

One exemplary processing apparatus manufactured in accordance with the principles of the present invention is shown in FIGS. 1 and 2, where FIG. 1 is a top view of one exemplary processing apparatus 10, and FIG. 2 shows a process array 20. An enlarged view of a portion of the processing apparatus 10 that includes. Any other shape that can be rotated may be used instead of the circular disk, but the processing apparatus 10 may preferably be a circular disk shape as shown in FIG. It may be desirable for the processing device 10 to be a self-contained unitary item that can be transported separately from a system in which the processing device 10 can be used.

It may be desirable for the processing device 10 to be able to rotate about an axis of rotation that preferably coincides with the center 12 of the processing device 10. It may be desirable for the axis of rotation to be generally perpendicular to the opposing major faces of the processing apparatus 10, but such an arrangement may not be required. In some embodiments, the center 12 of the processing device 10 may include an opening sized to receive a spindle that may extend therethrough.

The processing device 10 comprises at least one, preferably a plurality of process arrays 20. If the processing apparatus 10 is circular as shown, it may be desirable for each of the illustrated process arrays 20 to extend from the vicinity of the center 12 of the processing apparatus 10 toward the periphery of the processing apparatus 10. have. It may be desirable for the process array 20 to be substantially radially aligned with respect to the center 12 of the processing apparatus 10 (wherein “substantially radially aligned” is the processing apparatus 10). Means generally aligned along a radius 21 extending outwardly from the center 12 of. While this arrangement may be desirable, it will be appreciated that any arrangement of process array 20 may alternatively be used. Also, while the illustrated processing apparatus 10 includes one process array 20, it will be appreciated that two or more process arrays 20 may be provided in the processing apparatus 10.

Exemplary process array 20 (in the illustrated embodiment) includes a loading chamber 30 coupled to chamber 40 along conduit 32. The process array 20 also includes a heat transfer structure in the form of two heat transfer chambers 42 and 44 connected to the chamber 40 by conduits 41 and 43, respectively.

It should be understood that multiple features associated with the example process array 20 shown may be optional. For example, the loading chamber 30 and associated conduits 32 may be optional, in which case the analyte may be introduced directly into the chamber 40 either directly or through a different loading structure. At the same time, additional features may be provided to the process array 20. For example, two or more loading chambers and separate conduits leading to the chambers may be associated with the process array according to the present invention. Other features, such as valves, filters, beads, and the like, may also be provided in the process arrays of the present invention, some of which may be described herein in connection with other exemplary embodiments.

Any loading structure provided in connection with process array 20 may be designed to mate with an external device (eg, a pipette, hollow syringe, or other fluid delivery device) for receiving an analyte. The loading structure itself may define a predetermined volume (eg, as the loading chamber 30 of FIG. 1 does), or the loading structure does not define a specific volume but instead is a predetermined location at which an analyte is introduced. Can be. For example, the loading structure may be provided in the form of a port into which a pipette, needle or the like is inserted or attached. In one embodiment, the loading structure may be a designated location along a conduit adapted to receive a pipette, syringe needle, or the like, for example. Loading may be performed manually or by an automated system (eg robotic or the like). In addition, the processing device 10 may be loaded directly from another device (using an automated system or manually).

3 is an enlarged cross-sectional view of the processing apparatus 10 taken along line 3-3 of FIG. Although the processing apparatus of the present invention can be manufactured using any of a number of suitable construction techniques, one exemplary configuration can be seen in the cross-sectional view of FIG. 3. The illustrated processing apparatus 10 includes a base layer 14 attached to one major surface of the core layer 16 (the major surface is for example facing the viewer in the top view of FIG. 1). A cover layer 18 is attached to the core layer 16 over the major surface of the core layer 16 facing away from the base layer 14.

The layers of the processing apparatus 10 may be made of any suitable material or combination of materials. Examples of some materials suitable for the base layer 14 and / or core layer 16 include, but are not limited to, polymeric materials, glass, silicon, quartz, ceramics, and the like. In the case of the processing apparatus 10 in which the layers are in direct contact with the analyte, the reagent, etc., it may be desirable for the material or materials used for the layers to be non-reactive with the analyte, the reagent, and the like. Examples of some suitable polymeric materials that may be used for the substrate in many different bioanalytical applications may include polycarbonate, polypropylene (eg, isotactic polypropylene), polyethylene, polyester, and the like. This is not restrictive.

It may be desirable for base layer 14 and / or cover layer 18 to be made of a material that enables detection of one or more properties of analyte in chamber 40. Such detection may enable qualitative and / or quantitative analysis. Detection may preferably be accomplished using selected light, where the term “light” refers to electromagnetic energy, whether visible or invisible to the human eye. It may be desirable for the light to be in the range of ultraviolet to infrared electromagnetic energy, and in some cases it may be desirable for the light to include electromagnetic energy in the visible spectrum of the human eye. Moreover, the selected light can be, for example, light of one or more specific wavelengths, one or more ranges of wavelengths, one or more polarization states, or a combination thereof.

Regardless of the component (eg, cover layer 18 and / or base layer 14) from which the detection takes place, the material used preferably transmits a substantial portion of the selected light. For the purposes of the present invention, a substantial portion may be, for example, at least 50% of the vertically incident selected light, more preferably at least 75% of the vertically incident selected light. Examples of some materials suitable for the detection window include, for example, polypropylene, polyester, polycarbonate, polyethylene, polypropylene-polyethylene copolymers, cyclo-olefin polymers (eg polydicyclopentadiene), and the like. Including but not limited to.

In some cases, the base layer 14 and / or cover layer 18 of the processing device 10 are opaque such that the processing device 10 has a volume of the chamber 40 and at least one side of the processing device 10. It may be desirable to be opaque in between. Opaque means that transmission of the selected light described above is substantially prevented (eg, 5% or less of such vertically incident light is transmitted).

The components that make up the processing apparatus 10 may be attached to each other by any suitable technique or combination of techniques. Suitable attachment techniques preferably have sufficient integrity such that the attachment can withstand the forces encountered during processing of the analytes in the chamber. Some examples of suitable attachment techniques include, for example, adhesive attachment (using pressure sensitive adhesives, curable adhesives, hot melt adhesives, etc.), heat sealing, heat welding, ultrasonic welding, chemical welding, solvent welding, Extrusion, extrusion casting, mechanical attachment (eg, friction-fit, etc.), and combinations thereof. Also, the techniques used to attach different layers can be the same or different. For example, the technique or techniques used to attach the base layer 14 and the core layer 16 may be the same or different from the technique or techniques used to attach the cover layer 18 and the core layer 16. Can be. Several potentially suitable attachment techniques can be described in the patent literature referred to herein.

While various layers and components are shown in homogeneous construction in the cross-sectional views of various exemplary processing apparatus, it should be understood that various components may be comprised of more than one material / layer. In addition, in some processing apparatuses, multiple components can potentially be combined into a single article to reduce the number of components that must be attached to manufacture the processing apparatus.

4A and 4B show one exemplary process in which analytes are thermally transferred within the illustrated process array. As shown in FIG. 4A, analyte 46 is located in chamber 40. As discussed herein, analyte 46 may preferably be transferred from loading chamber 30 through conduit 32 into chamber 40. Transfer from the loading chamber 30 to the chamber 40 through the conduit 32 may preferably be accomplished by rotating the processing device 10 or under the influence of gravity.

After the analyte 46 is located in the chamber 40, the transfer of the heat transfer structure to the heat transfer chambers 42, 44 may preferably be accomplished by temperature control as discussed herein. For example, when the processing device 10 is rotated to move the analyte 46 into the chamber 40, the analyte 46 in the chamber 40 enters the heat transfer chambers 42 and 44. If the dimensions of the conduits 41 and 43 are selected to prevent, heat-driven transmission may be necessary. In such embodiments, the physical dimensions of at least a portion of the conduits 41, 43 are such that the conduits 41, 43 may have a pressure difference (eg, between chamber 40 and one or both of chambers 42, 44). , Heat-driven vacuum) may be selected to prevent flow.

1 and 2, the processing apparatus 10 is preferably in the form of a ring having an outer diameter 51 and an inner diameter 52 in the processing apparatus 10, which is preferably circular in shape. It may include the structure 50. The heat transfer structure 50 may preferably be in the form of a metal foil layer or other material that may be used, for example, to transfer thermal energy into and / or out of the chambers 40, 42, 44. Such a foil layer may in some cases be included within the base layer 14 of the composite structure shown in FIG. 3.

In order to deliver the analyte 46 to the heat transfer chambers 42, 44, it may be desirable to change the temperature of the retention fluid in the chambers 42, 44 from an onset temperature to a second temperature above the onset temperature. As the temperature of the dwelling fluid is raised to the second temperature, the volume of the dwelling fluid in the chambers 42, 44 increases, so that a portion of the dwelling fluid passes from each chamber 42, 44 through the conduits 41, 43. Pressurized into chamber 40.

The retention fluid in the heat transfer structure of the process array according to the invention can be a gas, a liquid or a combination thereof. In some cases, where the retention fluid comprises both gas and liquid (eg, the retention fluid may include air and water), heat transfer may be improved. The addition of materials such as water, hydrogels, etc., which can change phase during the heat transfer process (eg, transition between liquid and gas), results in a greater increase in volume when heated (compared to heating only gas). By providing a heat transfer can be improved. A greater increase in the volume of the retention fluid can provide a corresponding larger vacuum amount for moving the fluid through the system as the heated gas cools (and possibly returns to the liquid phase).

Such phase change-enhanced delivery may be advantageous when two or more heating / cooling cycles are used to deliver the fluid. As the amount of liquid changing phase during the process increases, the volume of fluid to be transferred may also preferably increase. Thus, only a small amount of fluid can be delivered by the initial heating / cooling cycle, but the amount of fluid delivered can be increased by each successive cycle. In essence, an initial delivery cycle can be considered to “priming” the system for more efficient delivery.

Residual fluids in different heat transfer chambers 42, 44 may be the same or different. While the retention fluid in the heat transfer chambers 42, 44 may include air as its gaseous component, alternatively other gases (eg, nitrogen, etc.) may be provided as the retention fluid in the chambers 42, 44. have.

After being heated to the second temperature, the retaining fluid in the heat transfer chambers 42, 44 may be reduced to a third temperature, preferably lower than the second temperature. The third temperature at which the retention fluid in the chambers 42, 44 is reduced after being heated to the second temperature may be equal to, lower than, or higher than the onset temperature.

As the temperature of the retention fluid remaining in the heat transfer chambers 42 and 44 is lowered toward the third temperature (from the second temperature), the volume of the retention fluid in the heat transfer chambers 42 and 44 decreases. Such reduction in volume preferably provides a vacuum (ie, pressure differential) that draws or moves at least a portion of the analyte 46 into the heat transfer chambers 42, 44 (as shown in FIG. 4B). The vacuum force may in some cases be supplemented by centrifugal force or gravity generated by rotating the processing device 10.

In some cases, analytes may be evenly distributed between chamber 40 and heat transfer chambers 42, 44 as shown between FIGS. 4A and 4B (analyte 46 as shown in FIG. 4A). Approximately one-third of) is found in each chamber 40, 42, 44 as shown in FIG. 4B). In other cases, the distribution of analyte between the chamber and any connected heat transfer chambers may not be even. Heating and cooling of the retention fluid in the heat transfer chambers 42, 44 may be performed in two or more consecutive heating and cooling cycles, for example, if a single cycle of heating and cooling does not provide the required amount of mass transfer. have.

Heating discussed herein is described, for example, in US Pat. No. 6,734,401 B2 (Beddingham et al.); US Patent Application Publication No. 2007-0009391 A1 (Application No. 11 / 174,680), entitled "Compliant Microfluidic Sample Processing Discs" (COMPLIANT MICROFLUIDIC SAMPLE PROCESSING DISKS); In a chamber in accordance with the principles discussed in US Patent Application Publication No. 2007-0010007 A1 (Application No. 11 / 174,757), entitled "SAMPLE PROCESSING DEVICE COMPRESSION SYSTEMS AND METHODS." It may be accomplished using any suitable technique, such as transferring heat energy into the retention fluid. The cooling described herein may also be achieved preferably according to the principles discussed in the above mentioned documents (eg, by convection when the processing device is rotated, by a Peltier element, etc.).

 Another process array in which the heat transfer principles of the present invention may be implemented is shown in FIG. 5. The illustrated process array includes a series of chambers 140a, 140b, 140c. All or just some of the chambers may be located within the temperature-controlled portion 150 of the processing apparatus (in FIG. 5 all chambers are located within the temperature-controlled portion 150). See, eg, US Pat. No. 6,734,401 B2 (Beddingham et al.); In accordance with the principles discussed herein, such as "COMPLIANT MICROFLUIDIC SAMPLE PROCESSING DISKS" and discussed in US Patent Application Publication No. 11 / 174,680 filed July 5, 2005 (Agent Control Number 60876US002). It may be desirable for all of the chambers connected in series to be positioned so that they are in the annular ring of the processing apparatus which can be heated. The cooling described herein may also be achieved preferably according to the principles discussed in the above-mentioned documents (eg, by convection when the processing device is rotated, by the use of compressed gas, Peltier elements, etc.).

The chambers 140a, 140b, 140c shown are connected in series with each other (although it may be useful to isolate the chambers by one or more valves as discussed in connection with other embodiments herein). The first chamber 140a may be supplied by a conduit 132 which may preferably be led from a loading chamber or other loading structure into which an analyte or other fluid may be introduced into the process array. The conduit 132 enters the first chamber 140a through the inlet port 142a from the general direction of the axis of rotation, for example, in which the processing device can be rotated about it to aid processing. The axis of rotation may preferably be located on or near radius 101 in a direction generally indicated by arrow 102, while chambers 140a, 140b, 140c are generally in the direction of arcuate arrow 104. Proceed. The direction indicated by arrow 102 may also be referred to as an upstream direction, as the device with the chamber 140 rotated therein will be rotated with the denser fluid to be referred to the opposite direction (downstream direction). Will tend to move). Arrow 102 and the upstream direction will be understood to be opposite to gravity in a method / system in which rotation is not required.

In the embodiment of Figure 5, the second and third chambers 140b, 140c form a heat transfer structure that is used to perform heat transfer in accordance with the principles of the present invention. The second chamber 140b may be connected to the first chamber 140a, preferably via a delivery conduit 141a, and the second chamber 140b is preferably via a delivery conduit 141b, a third chamber 140c. ) Can be connected. Because heat transfer techniques can be used to move the fluid through the chambers 140a, 140b, 140c, the chambers must be positioned continuously so as to be further away from the axis of rotation (or further downstream in the direction of gravity acting on the device). It doesn't have to be.

As the temperature of the fluid in the chamber changes, the fluid can be transported thermally between them. For example, the analyte may be delivered into the first chamber 140a such as by rotating a processing device including the chamber 140a such that the analyte flows into the first chamber 140a by centrifugal acceleration. Once in the first chamber 140a, the analyte can be processed, for example, to remove unwanted material, amplify selected genetic material, and the like.

At some point, the analyte in the first chamber 140a may be delivered to the second chamber 140b via a conduit 141a that preferably connects the first chamber 140a and the second chamber 140b. . Because the conduit 141a and the second chamber 140b are located upstream or closer to the axis of rotation than the outlet port 143a into which the fluid analyte passes through and into the delivery conduit 141a, only the rotation or gravity of the process array Will not be able to transfer fluid from the first chamber 140a to the second chamber 140b. In such situations, the heat transfer technology of the present invention can be used to perform fluid transfer.

With the fluid analyte positioned in the first chamber 140a, the retention fluid in the second chamber 140b and the third chamber 140c is heated to a second temperature that is higher than the onset temperature. As the temperature of the retention fluid in the second chamber 140b and the third chamber 140c increases, the volume of the retention fluid increases so that a portion of the retention fluid moves into the first chamber 140a (port 143a). Through). When heating occurs while the processing device is rotating or under the influence of gravity, as discussed herein, the analyte in the first chamber 140a may be the radial distal end 145a of the first chamber 140a (ie, , End of the first chamber 140a located farthest from the axis of rotation. If analyte is present in the port 143a when the heated retention fluid moves from the conduit 141a into the first chamber, the retention fluid will pass through the analyte in the first chamber 140a.

After a portion of the retention fluid moves through the port 143a into the first chamber 140a, the retention fluid remaining in the second chamber 140b and the third chamber 140c may be cooled to a third temperature. As the retention fluid cools to the third temperature, the volume of the retention fluid in these chambers decreases, thus preferably passing a portion of the analyte in the first chamber 140a through the delivery conduit 141a to the second chamber 140b. Create a vacuum to move or aspirate into.

The analyte sucked from the first chamber 140b through the conduit 141a passes through the port 142b located at the radial proximal end (upstream) of the second chamber 140b closest to the axis of rotation. Enter The delivery conduit 141a exits from the first chamber 140a via a port 143a located at a radial end (downstream) from the port 142b to which the delivery conduit 141a is connected to the second chamber 140b. It should be noted that In other words, the port 142b is located closer to the axis of rotation of the processing device than the port 143a.

As shown in FIG. 5, the port 143a to which the delivery conduit 141a is connected to the first chamber 140a is located closer to the axis of rotation than the distal end 145a of the first chamber 140a. Although the port (such as port 143a) is located closer to the axis of rotation than the radial distal end 145a or downstream of the chamber 140a, the radial proximal end of the chamber 140a (as does port 142a) or In a situation not located upstream, the port 143a may be described as being located in an "intermediate location" of the chamber (or other structure). In other words, the intermediate position along the chamber or conduit is not closest to or farthest from the axis of rotation with respect to the chamber or conduit in the rotary system and is neither upstream nor downstream end within the non-rotating gravity system.

When the processing device is rotated about the axis of rotation (or drawn in that direction in the gravity system), the denser constructs (e.g., liquid, beads, etc., as compared to gases in general) may be used as the first. Will move toward the radial distal end 145a of the chamber 140a. Because the port 143a is located in the distal end 145a of the first chamber 140a or in an intermediate position closer to the upstream end than downstream, the composition of the analyte collected at the distal end 145a is typically drawn into the delivery conduit 141a. (Because the components will be positioned beyond port 143a to a position that is more radially distal or downstream).

A portion of the analyte delivered into the second chamber 140b is delivered to the third chamber 140c by a heat transfer process similar to that used to transfer the analyte from the first chamber 140a to the second chamber 140b. Can be. In delivery, the heated dwelling fluid in the third chamber 140c moves into the second chamber 140b through the delivery conduit 141b. The delivery conduit 141b opens at one end through the port 143b into the second chamber 140b and at the opposite end through the port 142c into the third chamber 140c. Similar to the delivery conduit 141a, the port 142c leading into the third chamber 140c is closer or more closer to the axis of rotation of the processing device than the port 143b (through which fluid enters the delivery conduit 141b). Located upstream. In addition, since the port 143b is located at an intermediate position (for example, closer to the rotation axis than the distal end 145b of the second chamber 140b), the analysis collected at the distal end 145b of the second chamber 140b. The composition of water will typically not be drawn into delivery conduit 141b.

When combined with rotational processing techniques or gravity, heat transfer of the fluid within the process array can be used to achieve more complex processing sequences that are not possible with known processing devices. An example of a more complex processing sequence will now be described with respect to the process array shown in FIG.

The example process array of FIG. 6 is preferably provided in a processing apparatus designed for rotation about the axis of rotation located on or near the radius 201 located in the direction of the arrow 202. When rotated about the axis of rotation, the features of the process array will generally travel in the direction indicated by the arcuate arrow 204. Alternatively, the process array of FIG. 6 may be used in a non-rotating gravity based device where arrow 202 indicates an upstream direction, i. have.

The example process array includes a loading structure 230 that is connected with the first chamber 240 through a conduit 232. Chamber 240 includes a downstream or radial distal end 245 through which material is moved therein when a processing device including a process array is rotated about an axis of rotation or actuated by gravity. As such, the terms "upstream" and "downstream" may also be used when referring to directions with respect to the process array of FIG. More specifically, the direction indicated by arrow 202 may be referred to as upstream and the opposite direction may be referred to as downstream.

The process array also includes a heat transfer structure that assists in the heat transfer of the fluid through the chamber. In the example embodiment shown in FIG. 6, the heat transfer structure includes a trap chamber 260 in fluid communication with the chamber 240 via a transfer conduit 262. The heat transfer structure also includes a heat drive chamber 270 in fluid communication with the trap chamber 260 through drive conduits 272.

The delivery conduit 262 preferably includes a portion of the delivery conduit 262 upstream between the delivery port, where the delivery conduit is connected to the chamber 240, and the trap chamber 260 (or the thermal drive chamber 270). And a fluid trap 263 running in the direction. The fluid trap 263 effectively prevents fluid from moving from the chamber 240 to the trap chamber 260 or the thermal drive chamber 270 by rotation of the device including the process array under the influence of gravity or the like.

In use, the illustrated heat transfer structure can be used to transfer fluid from chamber 240 into trap chamber 260. Thus, trap chamber 260 can function as a reservoir for fluid removed from chamber 240. It may be desirable for trap chamber 260 to have a volume large enough to accommodate multiple fluid transfers from chamber 240. The volume of the trap chamber 260 may preferably be greater than or equal to the volume of the chamber 240. In some cases, it may be desirable for the volume of trap chamber 260 to be one and a half times (1.5) times the volume of chamber 240.

Heat transfer of the analyte can be achieved according to the principles discussed above. However, one difference can be seen at the remote location of the thermal drive chamber 270. It may be desirable for the thermal drive chamber 270 to be located in an area 250 of the thermally controlled processing device, for example, an area that can be selectively heated and / or cooled. If the processing apparatus is in the form of a circular disk, the region 250 may preferably be in the form of an annular ring (its arcuate portion is shown in FIG. 6).

The thermal drive chamber 270 is positioned away from the rest of the process array, but it is in fluid communication with the chamber 240 through the trap chamber 260, and ultimately the conduits 272, 262. In order to perform heat-driven transfer of fluid from chamber 240 to trap chamber 260, the retention fluid in drive chamber 270 may preferably be heated such that its temperature increases from the starting temperature to the second temperature. . As the temperature of the retention fluid in the drive chamber 270 increases, its volume also increases. Such an increase in volume pressurizes a portion of the retention fluid in thermal drive chamber 270 into conduit 272, and then presses a portion of the retention fluid in conduit 272 into trap chamber 260. Correspondingly, a portion of the retention fluid in trap chamber 260 is pressurized into delivery conduit 262. Residual fluid in the delivery conduit 262 is then pressurized into the chamber 240.

Any fluid in chamber 240 to be delivered to trap chamber 260 is located at or upstream of the delivery conduit 262 into chamber 240 (eg, closer to the axis of rotation). It may be desirable. Centrifugal force and / or gravity can preferably move or aspirate fluid in chamber 240 downstream or radially distal end 245 of chamber 240 such that delivery conduit 262 is directed to chamber 240. The port to be connected is covered by the fluid. The result is that the retention fluid pressurized from conduit 262 into chamber 240 preferably passes through the analyte in chamber 240.

After the retention fluid in the heat transfer structure (in the illustrated embodiment, including conduits 262 and 272 together with trap chamber 260 and heat drive chamber 270) is pressurized into chamber 240, the heat drive chamber The temperature of the retaining fluid remaining in 270 may preferably be reduced from the second temperature to the third temperature. As the retention fluid in the heat drive chamber 270 cools, its volume preferably decreases, which is through the conduit 272 to the trap chamber 260 and through the trap chamber 260 to the delivery conduit 262. Create a vacuum in communication. The vacuum then proceeds through the delivery conduit 262 to the chamber 240 so that the fluid present in the connection between the chamber 240 and the delivery conduit 262 is drawn into the delivery conduit 262. At least a portion of the fluid moved or drawn into the delivery conduit 262 from the chamber 240 is then delivered to the trap chamber 260, where it is preferably deposited.

The geometry of the trap chamber 260, together with the delivery conduits 262 and the thermal drive conduits 272, allows fluid transferred from the chamber 240 into the trap chamber 260 to remain within the trap chamber 260 and to provide a thermal drive chamber ( 270) may be desirable. Isolation of the thermal drive chamber 270 from the fluid transferred into the trap chamber 260 provides for the ability of the thermal drive chamber 270 to be used to transfer fluid two or more times from the chamber 240 into the trap chamber 260. I can keep it.

It may also be desirable for the material in the trap chamber not to be directly heated during the heat transfer process. Isolation of the trap chamber 260 is such that a conduit in fluid communication with the trap chamber 260 enters into the trap chamber 260 at or near its radial proximal or upstream end (ie, the end closest to the axis of rotation) and And / or exit therefrom. In such a configuration, for example, when the delivery conduit 262 and the drive conduit 272 are connected to the trap chamber 260 at a position located radially proximal or upstream of the trap chamber 260 (eg, a processing apparatus During rotation or under the influence of gravity) fluid entering the trap chamber 260 tends to move downstream or radially toward the end of the trap chamber 260 (i.e., in the direction opposite to the arrow 202). As such, most of the fluid entering the trap chamber 260 (preferably substantially all of the liquid) does not enter the drive conduit 272. Trap chamber 260 and / or delivery conduit 262 may also provide a structure (eg, a tendency to direct fluid entering the trap chamber 260 from chamber 240 downward into the main volume of trap chamber 260). For example, baffles, and the like.

As with the delivery conduit 262 of the process array of FIG. 6, the delivery conduit 262 may include a portion of the delivery conduit 262 (when moving from the chamber 240 toward the thermal drive chamber 270). It also includes a fluid trap 263 running in an upstream direction between the drive chambers 270. Such a fluid trap 263 effectively prevents fluid from moving from the first chamber 240 to the thermal drive chamber 270 by gravity or by rotation of an apparatus comprising a process array.

Even when the fluid trap 263 reaches the height of the radial base of the chamber 240 and the chamber is completely filled with the analyte, only the rotation of the device causes the analyte to pass through the fluid trap 263 and the trap chamber ( It may be desirable not to move into either 260 or the thermal drive chamber 270.

Another optional feature shown in the example process array of FIG. 6 includes a second chamber 280 that can be placed in fluid communication with chamber 240 via conduit 282. Conduit 282 is shown connected with chamber 240 at a radially distal point of chamber 240. Conduit 282 may alternatively be connected to chamber 240 at any selected location along the radial length of chamber 240, where the radial length is a dimension of chamber 240 along radius 201. Can be. The second chamber 280 can be used, for example, to supply cleaning fluid to the chamber 240.

Another optional feature shown in connection with the example process array of FIG. 6 is a valve structure used to control the flow of fluid from the second chamber 280 into the conduit 282. In the illustrated process array, any suitable alternative valve may be used in place of the illustrated valve structure, although the valve structure may include a valve lip 284 (see FIG. 7) extending into the volume of the second chamber 280. Shown).

7 is a cross-sectional view of a portion of a processing apparatus including a second chamber 280. As can be seen in FIGS. 6 and 7, the valve lip 284 is preferably located in the area occupied by the second chamber 280 on the processing device, ie the protruding chamber area. The protruding chamber region may preferably be formed by projecting the chamber boundary onto any one of the major faces of the processing apparatus.

In the embodiment shown in FIG. 7, the core layer 214 forms the first major face 215 of the processing apparatus facing away from the valve layer 216. The valve layer 216 is attached to the surface of the core layer 214 facing away from the first major face 215. The cover layer 218 is attached to the surface of the valve layer 216 facing away from the core layer 214, with the cover layer 218 facing away from the first major face 215 of the processing apparatus. The main face 219 is formed.

The valve lip 284 is shown extending into the protruding chamber region defined by the outermost boundary of the second chamber 280. Since the valve lip 284 is located within the protruding chamber area, the valve lip 284 is described as protruding over a portion of the second chamber 280 or cantilevering over a portion of the second chamber 280. Can be.

The valve lip 284 preferably forms a valve chamber 285 that may be at least partially positioned within the valve lip 284, as can be seen in FIG. 7. Valve chamber 285 is preferably in open fluid communication with conduit 282 leading to chamber 240. As such, any fluid entering the valve chamber 285 may enter the conduit 282 for delivery to the chamber 240.

At least a portion of the valve chamber 285 may preferably be located between the second major face 219 and at least a portion of the second chamber 280. The valve chamber 285 is also isolated from the second chamber 280 by a valve partition 286 that preferably separates the valve chamber 285 from the second chamber 280, thereby reducing the volume of the second chamber 280. Some of them lie between the valve septum 286 and the first major face 215 of the processing apparatus. In the illustrated embodiment, the cover layer 218 is preferably sealed to the valve lip 284 along the surface 283 to isolate the valve chamber 285 from the second chamber 280.

The valve septum 286 is preferably formed of a material whose opening can be formed by a non-contact method such as laser ablation, focused optical heating, or the like. Since such openings formed in the valve partition are typically irreversible (ie, the openings cannot be closed after formation), the valve structure shown in FIGS. 6 and 7 can be described as a "disposable" valve. The energy used to form an opening in the valve partition 286 can be directed onto the valve partition 286 through either the cover layer 218 or the core layer 214 (or both). However, energy is passed through the cover layer 218 to the valve septum 286 to avoid problems that may be associated with directing energy through the material in the second chamber 280 before reaching the valve septum 286. May be preferred.

One method of using the second chamber 280 to deliver fluid to the chamber 240 of the process array of FIG. 6 will now be described. After the selected fluid material is provided to the second chamber 280, an opening may be formed in the valve partition 286 at a desired position. One example is the opening 287a shown in FIG. 6. When the processing device including the second chamber 280 is rotated about gravity or rotated in the direction of the arrow 204, the fluid in the second chamber 280 draws the opening 287a from the second chamber 280. Through the valve chamber 285 and then into the conduit 282 for delivery to the chamber 240.

Since substantially all of the fluid located above the dashed line extending through the opening 287a will preferably move out of the second chamber 280, the position of the opening or openings formed in the valve septum 286 determines the selected volume of fluid. It may be selected to deliver to the chamber 240. For example, after initial delivery of fluid through opening 287a, a second volume of fluid in second chamber 280 may be delivered by forming second opening 287b in valve septum 286. After opening 287b is provided, a separate volume of fluid between two dashed lines extending through openings 287a and 287b may be transferred into chamber 240. 6 also includes a third opening 287c of the valve septum 286 through which substantially all fluid in the second chamber 280 can enter and enter the conduit 282 for delivery to the chamber 240. .

Fluid to be delivered from the second chamber 280 to the chamber 240 may be provided to the second chamber 280 when the processing device is manufactured or by the end user (or intermediate sector). Fluid may be delivered directly into the second chamber 280. Alternatively, fluid may be delivered to the second chamber via an optional loading structure 281 in fluid communication with the second chamber 280. The loading structure 281 may be used one or more times to deliver one or more discrete volumes of material to the second chamber 280.

One potential use for the second chamber 280 with the disposable valve structure shown in FIGS. 6 and 7 in fluid communication with the chamber 240 is, for example, washing fluid (salt water, etc.) or preferably one or more. It is to provide some other fluid that can be metered into the chamber 240 in a separate volume. By forming one or more openings in the valve partition 286 at one or more selected locations, the separated volume of the fluid (typically liquid) contained in the second chamber 280 is reduced from the second chamber 280 to the chamber 240. Can be delivered.

Continuous delivery of the separated volume from the second chamber 280 to the chamber 240 may be used to provide a “wash” solution, for example, which may remove undesirable substances from the chamber 240. For example, after delivery of the first volume of wash solution from the second chamber 280 to the chamber 240 (eg, through the opening 287a), it is desirable (such as in a dissolved state, incorporated therein). A portion of the wash solution with the undesired material may be removed from the chamber 240 using a heat transfer structure, where unnecessary portions are delivered to the trap chamber 260 as described herein. Such a washing step can be repeated if a sufficient volume of washing solution is in the second chamber 280. For example, second opening 287b may be formed to deliver a second volume of wash solution to chamber 240.

In another exemplary method using a process array similar to that shown in FIGS. 6 and 7, one or more reagents are in the second chamber 280 (eg, dried-down, etc.) or in a second in a liquid. One or more reagents may be delivered to chamber 280, through conduit 282, to chamber 240.

Another exemplary process array that may be provided to the processing apparatus according to the present invention is shown in FIG. 8. The example process array of FIG. 8 is preferably provided in a processing apparatus designed for rotation about an axis of rotation that may be located on or near the radius 301 in the direction of the arrow 302. When rotated about the axis of rotation, the features of the process array will generally travel in the direction indicated by the arcuate arrow 304. Alternatively, the process array of FIG. 8 may be used in a non-rotating gravity based device in which the arrow 302 indicates an upstream direction, ie opposite the direction of gravity acting on the process array (when the direction of gravity is downstream). have.

The example process array includes a first chamber 340, which is connected with the second chamber 360 through a conduit 332. The first chamber 340 and the second chamber 360 may preferably be arranged on the processing apparatus to define the upstream and downstream directions. The upstream direction is the direction when moving from the second chamber 360 toward the first chamber 340 (the general direction is indicated by arrow 302). The downstream direction is a direction when moving from the first chamber 340 toward the second chamber 360. It may be desirable for the upstream and downstream directions to be substantially radially aligned with the center of the processing device such array is located in the case of a rotating system or aligned with gravity in the gravity system.

First chamber 340 preferably includes a disposable valve 342 that prevents fluid from passing into conduit 332 until open. The valve 342 may take the form of a bulging valve lip as discussed above with respect to FIG. 7. The first chamber 340 includes a radial end or downstream end 345 through which material is moved therein when a processing device including a process array is rotated about a rotation axis or subjected to gravity. The first chamber 340 also preferably includes a loading structure 330 through which the analyte can be introduced into the first chamber 340. In the illustrated embodiment, the first chamber 340 also includes an optional reagent 341 that can be used for processing.

The second chamber 360 is preferably an area of the processing device that can be thermally controlled, eg, heated and / or cooled, to change the temperature of the analyte or other material located within the second chamber 360. 350 may be located. If the processing apparatus is in the form of a circular disk, the region 350 may preferably be in the form of an annular ring, the arcuate portion of which is shown in FIG. 8. As a result, the second chamber 360 may provide analytes that require thermal control, such as, for example, isothermal processes, processes that require thermal cycling between two or more different temperatures (eg, PCR, etc.). Can be used for processing. The second chamber 360 shown includes an optional reagent 361 that can be used in connection with the treatment.

The process array shown in FIG. 8 also includes a heat transfer structure that facilitates heat transfer of the fluid through the first chamber 340. In the example embodiment shown in FIG. 8, the heat transfer structure includes a heat drive chamber 370 in fluid communication with the first chamber 340 via a transfer conduit 362. The thermal drive chamber 370 may preferably be located within the thermal control area 350 on the processing apparatus.

In use, the illustrated heat transfer structure can be used to transfer fluid from the first chamber 340 into the delivery conduit 362 and the drive chamber 370. Thus, the heat drive chamber 370 can function as a reservoir for fluid removed from the first chamber 340 (also provides a retention fluid used to perform heat transfer). It may be desirable for the thermal drive chamber 370 to have a volume large enough to accommodate multiple fluid transfers from the first chamber 340. The volume of the thermal drive chamber 370 may be, for example, preferably greater than or equal to the volume of the first chamber 340.

Heat transfer of the analyte (or other fluid) may be accomplished according to the principles discussed above in connection with the process array shown in FIG. 6. As in the transfer conduit 262 of the process array of FIG. 6, the delivery conduit 362 has a portion of the delivery conduit 362 (when moving from the first chamber 340 toward the thermal drive chamber 370). And a fluid trap 363 running upstream between the heat drive chamber 370. Such a fluid trap 363 effectively prevents fluid from moving from the first chamber 340 to the thermal drive chamber 370 by rotation of the device comprising the process array or under the influence of gravity.

The fluid trap 363 reaches a height that is radially higher (ie, closer to or upstream of the axis of rotation) than the height of any fluid located within the chamber 340, so that only by the rotation (or gravity) of the device It may be desirable for the analyte in chamber 340 not to move past fluid trap 363 and into thermal drive chamber 370. The height of the fluid trap 363 may vary depending on various factors, including, for example, the maximum height of the fluid in the chamber 340, the size of the delivery conduit 362, the hydrophobicity / hydrophilicity of the materials used to construct the process array, and the like. Can be.

The fluid trap 363 measures the height of the chamber 340 (the height of the chamber 340 is from its radial end or downstream end 345 to its radial proximal or upstream end, ie, the end located closest to the axis of rotation). It may be desirable to reach a height that is at least 25% or greater (measured in the upstream direction from the radial end or downstream end 345 of chamber 340). Alternatively, fluid trap 363 in delivery conduit 362 may reach a height that is preferably at least 50% or more of the height of chamber 340. In another alternative, the fluid trap 363 in the delivery conduit 362 may reach a height that is preferably at least 75% or more of the height of the chamber 340. In another alternative, the fluid trap 363 in the delivery conduit 362 may reach a height that is preferably at least 90% or more of the height of the chamber 340.

Any fluid to be delivered from the first chamber 340 is located in the chamber 340 at or upstream of the delivery port to which the delivery conduit 362 is connected to the first chamber 340 (ie, closer to the axis of rotation). It may be desirable. When the processing device is rotating about an axis of rotation as discussed above while the valve 342 is closed, the centrifugal force causes the fluid in the first chamber 340 to displace the radial or downstream end of the first chamber 340. Will be moved toward 345 such that the delivery port to which the delivery conduit 362 is connected to the first chamber 340 is covered by the fluid. If the system is not rotating, gravity can be used to move the fluid toward the downstream end 345 of the first chamber 340. The result is that any retaining fluid that is pressurized from the delivery conduit 362 into the first chamber 340 preferably passes through the analyte in the second chamber 340.

8 illustrates the positioning of the inlet port of the delivery conduit 362 into the side of the input chamber 340. After pipette metering, when the process array of FIG. 8 is stopped or slowed, the fluid meniscus may rise by surface energy (ie, in the direction of arrow 302), where the fluid meniscus is transferred to the delivery conduit. Extends above the input port into 362. In such a situation, the fluid in the input chamber 340 may move into the delivery conduit 362 by capillary action (ie, the lateral surface of the fluid is curved upwards in the chamber 340). Alternative positioning for the input port leading into the delivery conduit 362 will be more centered within the chamber 340 (ie, in the direction of the arrow 302), so that surface energy is transferred to the delivery conduit 362 when rotation is slowed. The fluid meniscus will be pulled away from the subsequent input port.

In some embodiments, it may be desirable to maintain a small amount of heat in the thermal drive chamber 370 when rotation is slowed or stopped. This can potentially provide an amount of outward pressure that prevents or reduces the likelihood of unnecessary fluid entering the delivery conduit 362.

In another embodiment, the trap furthest away in the upstream section of the fluid trap channel 363 (ie, arrow 302) to collect any fluid that may have entered the trap channel 363 when the rotation has stopped or slowed down. It may be desirable to place the expansion chamber in a section of channel 363. When rotation resumes, fluid collected in any such expansion chamber will then be moved back into input chamber 340. In addition, the expansion chamber or other geometry in the fluid trap channel 363 also creates an air gap that may help prevent or at least stop the unwanted capillary flow and siphoning of the fluid from the input chamber 340. The introduction can serve to separate the continuity of the fluid channel.

The meniscus height, discharge height, channel dimensions, fluid viscosity, fluid contact angle, rotational acceleration, differential pressure, fluid velocity and fluid density all control priming or siphoning of the input chamber 340 into the thermal drive chamber 370. Can contribute to When the process array of FIG. 8 is rotating, if the delivery conduit 362 and the fluid trap 363 section are filled with fluid lower than the surface of the fluid in the input chamber 340, the fluid in the input chamber 370 is siphoned. Will be emptied by Thus, the fluid drive chamber 370 is filled by differential pressure and by siphoning.

Another optional feature shown in the example process array of FIG. 8 includes a third chamber 380 that can be placed in fluid communication with the first chamber 340 via a conduit 382. Conduit 382 is shown connected with the first chamber 340 at an intermediate point of the second chamber 340. Conduit 382 may alternatively be connected to first chamber 340 at any selected location along the height of chamber 340 (in which case the height of the chamber is determined between the upstream and downstream ends).

Another optional feature shown in connection with the example process array of FIG. 8 is a disposable valve structure 386 used to control the flow of fluid from the third chamber 380 into the conduit 382. In the illustrated process array, the valve structure takes the form of a valve lip extending into the volume of the third chamber 380, which valve lip (similar to the valve structure described in connection with the process array shown in FIG. 6). An opening 387 may be formed to allow fluid to flow from the third chamber 380 into the conduit 382.

In addition to the third chamber 380, the process array can also include a subchamber 388 through which fluid from the third chamber 380 can be collected during use. Fluid collected in subchamber 388 may be delivered into intermediate chamber 390. Control of the delivery of fluid to the intermediate chamber 390 may be provided by the disposable valve 389.

For example, when the valve 389 is opened (after the subchamber 388 is filled with fluid), the fluid from the subchamber 388 is preferably intermediate, which may include one or more reagents 391. The chamber 390 may be entered. Reagent 391 may preferably react with or be absorbed by the fluid from subchamber 388. At a selected time, the disposable valve 392 in the intermediate chamber 390 can be opened. When the valve 392 is opened, fluid in the intermediate chamber may be delivered to the second chamber 360 through a conduit 393 in fluid communication with the process conduit 332.

Another exemplary process array that may be provided to the processing apparatus according to the present invention is shown in FIG. 9. The exemplary process array of FIG. 9 is preferably provided in a processing apparatus designed for rotation about an axis of rotation that may be located on or near the radius 401 in the direction of the arrow 402. When rotated about the axis of rotation, the features of the process array will generally travel in the direction indicated by the arcuate arrow 404. Alternatively, the process array of FIG. 9 may be used in a non-rotating gravity based device in which the arrow 402 represents an upstream direction, i.e., opposite the direction of gravity acting on the process array (when the direction of gravity is downstream). have.

The example process array of FIG. 9 is similar in many respects to the process array shown in FIG. 8, and includes a first chamber 440, a reagent 441 identified in the first chamber 340, a loading structure 430, a single use Features such as valve 442 and downstream end 445. In addition, the process array of FIG. 9 also has a second chamber 460 connected to the first chamber 440 by a process conduit 432, as well as an opening 487 through the conduit 482. A valve structure 486 and a third chamber 480 can be formed to deliver fluid to 440.

Also similar to the process array of FIG. 8, the process array of FIG. 9 also includes a transfer conduit 462 that connects the thermal drive chamber 470 to the first chamber 440. The thermal drive chamber 470 is preferably located within a thermal control region of the processing apparatus in which the process array is positioned to provide the thermal control necessary to perform heat transfer in accordance with the principles of the present invention. The delivery conduit 462 includes a fluid trap 463 that prevents fluid from moving from the first chamber 440 to the heat drive chamber 470 only through the rotation or gravity of the processing device.

A further feature shown in the process array of FIG. 9 is a valve 472 located along the delivery conduit 462. The valve 472 can be used to control the activation of the heat transfer function. For example, when valve 472 is closed, heating or cooling of the retention fluid in thermal drive chamber 470 will not function to pull or move fluid from first chamber 440. The exact position of the valve 472 is not critical, but it must be located between the first chamber 440 and the thermal drive chamber 470. Valve 472 may be a disposable valve similar to that described herein.

Another difference between the process array of FIG. 9 and the process array of FIG. 8 is that the process array of FIG. 9 does not include a subchamber and an intermediate chamber of the process array of FIG. 8. However, the process array of FIG. 9 includes a third chamber 490 located within the thermal control region 450 as in the second chamber 460. The second chamber 460 includes an optional reagent 461 located therein. The third chamber 490 also includes an optional reagent 491 located therein. Third chamber 490 is also connected to second chamber 460 via disposable valve 462 and conduit 492. Rotation or gravity of the processing device in which the process array of FIG. 9 is located will preferably move fluid from the second chamber 460 to the third chamber 490, where the third chamber 490 is a second chamber ( Located downstream of 460.

Another exemplary process array is shown in connection with FIG. 10, which illustrates another optional feature of the process array of the present invention. The exemplary process array of FIG. 10 is preferably provided in a processing apparatus designed for rotation about an axis of rotation that may be located on or near radius 501 in the direction of arrow 502. When rotated about the axis of rotation, the features of the process array will generally travel in the direction indicated by the arcuate arrow 504. Alternatively, the process array of FIG. 10 may be used in a non-rotating gravity based device in which the arrow 502 indicates an upstream direction, i.e., opposite the direction of gravity acting on the process array (when the direction of gravity is downstream). have.

The example process array of FIG. 10 is similar in many respects to the process arrays shown in FIGS. 8 and 9, and includes a first chamber 540, a loading structure 530 identified in the first chamber 540, a disposable valve ( 542 and downstream end 545. In addition, the process array of FIG. 10 also includes a second chamber 560 connected to the first chamber 540 by a process conduit 532.

In addition, similar to the process arrays of FIGS. 8 and 9, the process array of FIG. 10 also includes a transfer conduit 562 that connects the first chamber 540 to a pair of thermal drive chambers 570a, 570b. . Delivery conduit 562 also includes a fluid trap 563 thereafter branching delivery conduit 562 to delivery conduits 562a and 562b. Both thermal drive chambers 570a and 570b are preferably located in thermal control region 550.

Each of the delivery conduits 562a, 562b may preferably include valves 572a, 572b (respectively) that control the flow of fluid into and from the thermal drive chambers 570a, 570b. The valves 572a, 572b may preferably take the form of a disposable valve as described herein. In some cases, one of the thermal drive chambers may not be isolated from the first chamber 540 by a valve, and additional thermal drive chambers may be isolated using a valve. Also, although only two thermal drive chambers are shown in the process array of FIG. 10, three or more thermal drive chambers may be provided if desired. In another variation where multiple heat drive chambers are provided, each of the heat drive chambers may be connected to the chamber 540 using dedicated delivery conduits (instead of branching the conduits 562 as shown in FIG. 10).

The use of reagents in connection with the process array of the processing apparatus of the present invention is optional, ie the processing apparatus of the present invention may or may not include any reagents in the process array chamber. In other variations, some of the chambers in the various process arrays may include reagents, while others may not. In another variation, the various chambers may comprise different reagents. In addition, the interior of the chamber structure may be coated or otherwise treated to control the adhesion of reagents.

The process array used in the processing apparatus of the present invention may preferably be "unvented". As used in connection with the present invention, a “non-breathable process array” is a process array (ie, at least two connected chambers) in which only openings leading into the process array are located in the loading structure, eg the loading chamber. In other words, to reach the chamber within the process array of the non-breathable process array, the analyte must be transported directly into or into the loading structure. Similarly, any air or other fluid located within the process array prior to loading of the analyte must also be released from the process array through the loading structure. In contrast, the vented process array will include at least one opening on the outside of the loading structure. Such openings will allow the release of any air or other fluid located within the process array prior to loading.

Moving an analyte through a processing device comprising a non-breathing process array alternately accelerates and decelerates the device during rotation, essentially buffing the analyte through conduits and chambers in a rotating system (herein In addition to the heat transfer technology described in < RTI ID = 0.0 > Rotation may be performed using at least two acceleration / deceleration cycles, namely initial acceleration, followed by deceleration, second acceleration and second deceleration. If acceleration and / or deceleration is rapid, it may be more useful. The rotation may also preferably be in only one direction, ie it may not be necessary to reverse the direction of rotation during the loading process. Such loading process allows the analyte to displace air in portions of the process array located further from the center of rotation of the device. Actual acceleration and deceleration rates may vary based on various factors such as temperature, size of the device, distance of the analyte from the axis of rotation, material used to manufacture the device, characteristics of the analyte (eg, viscosity), and the like.

Although not shown, the chambers in the process array of the present invention may also include one or more optional mixing chambers that aid in the mixing of materials in the chambers. Their operation in mixing chambers and rotary processing devices is described, for example, in a US patent filed December 12, 2003 entitled "SAMPLE MIXING ON A MICROFLUIDIC DEVICE". Application Publication 2005-0129583 A1 (Agent Control Number 59072US002) may be described in more detail. Briefly, however, a mixing chamber provided in connection with a chamber in a rotary processing device may operate by varying the rotational speed of the processing device to move the analyte in the chamber into and from the mixing chamber to achieve mixing of the analytes.

Another variation of the processing apparatus of the present invention is shown in FIG. 11, wherein the processing apparatus 610 is constructed from a plurality of process modules 620 located within the frame 630. Frame 630 preferably defines a center 612, and process module 620 may be provided in a radial array around center 612. Each of the process modules 620 may include one or more process arrays formed therein. Further details regarding some potentially useful process modules and frames are described in a US patent application filed on July 5, 2005 entitled MODULAR SAMPLE PROCESSING APPARATUS KITS AND MODULES. Published 2007-0007270 A1 (Application No. 11 / 174,756).

As used in this specification and the appended claims, the singular forms "a", "an" and "the" include plural referents unless the content clearly dictates otherwise. Thus, for example, a reference to "one heat drive chamber" includes a plurality of heat drive chambers (unless clearly indicated otherwise), and reference to "chamber" may refer to one or more chambers and their equivalents known to those skilled in the art. Contains a reference to

All references and publications cited herein are expressly incorporated herein by reference in their entirety. Exemplary embodiments of the invention have been discussed and reference has been made to possible variations within the scope of the invention. These and other changes and modifications in the present invention will be apparent to those skilled in the art without departing from the scope of the present invention, and it should be understood that the present invention is not limited to the exemplary embodiments described herein. Accordingly, the present invention should be limited only by the claims and their equivalents provided below.

Cross Reference to Related Application

This application is incorporated by reference in the United States, filed Dec. 22, 2006, entitled THERMAL TRANSFER METHODS AND STRUCTURES FOR MICROFLUIDIC SYSTEMS, which is incorporated herein by reference in its entirety. 35 USC for patent application 60 / 871,611 Insist on benefits under § 119 (e).

Claims (25)

Providing a processing apparatus comprising at least one process array comprising a first chamber and a heat transfer structure comprising a retention fluid, wherein the heat transfer structure comprises a transfer conduit connected to the first chamber; Providing an analyte in the first chamber; The first portion of the retention fluid in the heat transfer structure is heated through the delivery conduit by heating at least a portion of the retention fluid in the heat transfer structure such that the volume of the retention fluid in the heat transfer structure increases to pressurize the first portion of the retention fluid into the first chamber. Passing it through the analyte in the chamber; And Cooling the heated dwelling fluid in the heat transfer structure after the first portion of the dwelling fluid has passed into the first chamber, wherein the volume of the dwelling fluid in the heat transfer structure is reduced such that at least a portion of the analyte in the first chamber is delivered. Drawn into the heat transfer structure through the conduit- And a fluid in the processing device. The method of claim 1, further comprising performing at least two consecutive heating and cooling cycles on the retaining fluid in the heat transfer structure. The method of claim 1, further comprising rotating the processing device about an axis of rotation while passing the first portion of the retention fluid to the analyte in the first chamber, wherein the rotation causes the analyte to be radius of the first chamber. Moving fluid toward the distal end thereof. The method of claim 3, wherein at least a portion of the delivery conduit is located closer to the axis of rotation than at least a portion of the first chamber. The heat transfer structure of claim 1, wherein the heat transfer structure includes a trap chamber in fluid communication with the transfer conduit, the heat transfer structure includes a heat drive chamber in fluid communication with the trap chamber through the drive conduit, and also through the transfer conduit. And a portion of the analyte drawn into the structure is deposited in the trap chamber. The method of claim 5, wherein the retention fluid in the trap chamber is not directly heated. 6. The method of claim 5, further comprising rotating the processing device about an axis of rotation, wherein the delivery conduit and drive conduit are connected to the trap chamber on the radial proximal side of the trap chamber, thereby trapping the processing device while rotating. The fluid entering the chamber is moved towards the radially distal side of the trap chamber so that most of the fluid entering the trap chamber does not enter the drive conduit, and the radial proximal side of the trap chamber is on the axis of rotation than the radial distal side of the trap chamber. Located closer, the method for delivering fluid within the processing device. 8. The method of claim 7, wherein substantially all of the liquid entering the trap chamber does not enter the drive conduit. The method of claim 1, further comprising rotating the processing device about an axis of rotation, wherein the delivery conduit is connected to the first chamber at the first port, the first port being radially occupied by the first chamber. Disposed in an intermediate position along the radial length along a radius extending from the axis of rotation. The fluid of claim 1, further comprising opening a valve located between the first chamber and the delivery conduit prior to passing the first portion of the retention fluid through the delivery conduit to the analyte. How to. The process chamber of claim 1, wherein the process array includes a second chamber and a second conduit extending between the second chamber and the first chamber, wherein the fluid is passed through the second conduit by rotating the processing device about an axis of rotation. And delivering from the first chamber to the first chamber. The process of claim 11, further comprising opening a second chamber valve positioned between the second chamber and the second conduit prior to transferring fluid from the second chamber to the first chamber via the second conduit. A method for delivering fluid in the device. 12. The processing apparatus of claim 11, wherein the processing device further comprises an intermediate chamber located between the second chamber and the first chamber along the second conduit, wherein the fluid transferred from the second chamber to the first chamber is fluid-filled with the first chamber. Passed to the intermediate chamber before reaching the intermediate chamber, wherein the intermediate chamber comprises a reagent located in the chamber, and the fluid contacts the reagent in the intermediate chamber before reaching the first chamber. The method of claim 13, further comprising opening an intermediate chamber inlet valve positioned between the intermediate chamber and the second chamber before passing the fluid from the second chamber to the intermediate chamber. Way. 15. The method of claim 14, further comprising opening an intermediate chamber outlet valve located between the intermediate chamber and the first chamber before passing the fluid from the intermediate chamber to the first chamber. Way. At least one process array formed in the body Including; The at least one process array, A first chamber; A second chamber; Process conduit extending between the first chamber and the second chamber, wherein the first chamber and the second chamber are upstream when moving from the second chamber toward the first chamber and when moving from the first chamber to the second chamber Defines a downstream direction of-; And A heat transfer structure comprising a heat drive chamber comprising a retention fluid and a transfer conduit extending between the first chamber and the heat drive chamber, wherein the transfer conduit enters the first chamber through the transfer port, the transfer conduit A portion of the fluid trap that travels in an upstream direction between the delivery port and the thermal drive chamber − Processing device comprising a. The apparatus of claim 16, wherein the fluid trap in the delivery conduit reaches at least a midpoint of the first chamber between the first chamber and the heat drive chamber. 17. The processing apparatus of claim 16, further comprising a valve positioned between the first chamber and the heat drive chamber, wherein fluid passage between the first chamber and the heat drive chamber through the delivery conduit is prevented until the valve is opened. . 17. The heat transfer structure of claim 16, wherein the heat transfer structure further comprises a trap chamber located along a transfer conduit between the first chamber and the heat drive chamber, wherein the trap chamber is located within the fluid trap or between the fluid trap and the heat drive chamber. Processing unit. The processing apparatus of claim 19, wherein the trap chamber is connected to the delivery conduit along an upstream end of the trap chamber. The apparatus of claim 16, wherein the heat transfer structure comprises two or more heat drive chambers, all of the two or more heat drive chambers being located downstream of the fluid trap in the transfer conduit. 22. The apparatus of claim 21, further comprising a valve positioned between each of the first chamber and the thermal drive chamber, wherein fluid passage between the first chamber and each of the thermal drive chambers through the delivery conduit is performed by the first chamber and the thermal drive chamber. A processing apparatus that is prevented until a valve located between the chambers is opened. The processing apparatus of claim 16, wherein the process conduit is coupled to the first chamber in a downstream direction from the delivery port. 17. The processing apparatus of claim 16, further comprising a valve positioned between the first chamber and the process conduit, wherein fluid passage from the first chamber to the second chamber through the process conduit is prevented until the valve is opened. 17. The processing apparatus of claim 16, wherein a plurality of process arrays are located within the body, wherein the process array is substantially radially aligned about the center of the body such that the upstream and downstream directions extend substantially radially from the center of the body.